Abstract
The objective of this study was to investigate the bioavailability (BA) and pharmacokinetics (PK) of doxycycline (DC) in channel catfish (Ictalurus punctatus) following a single intravenous injection at 5 mg/kg and a single oral administration at 50 mg/kg at 24°C. The calculation of PK parameters was based on the software 3P97. The plasma samples were determined using ultra-performance liquid chromatography. Following oral administration, the multiple-peak phenomenon presented in concentration vs. time curve of DC at 2 h (107.01 mg/L), 8 h (55.07 mg/L), and 72 h (15.10 mg/L), respectively. The compartmental model cannot simulate the oral concentration vs. time profile beside a non-compartmental model. The calculated parameters of the elimination rate constant (λz), the elimination half-life (t1/2λz), and the area under the concentration vs. time curve (AUC0-144) were 0.037 1/h, 18.91 h, and 2255.45 μg.h/mL, respectively. After intravenous administration, the concentration vs. time profile of DC was best described by a two-compartmental open model without absorption. The parameters of the distribution rate constant (α), the distribution half-life (t1/2α), the elimination rate constant (β), the elimination half-life (t1/2β), the apparent distribution volume at steady state (Vss), the total clearance (Cl) and the area under the concentration vs. time curve (AUC0-∞) were 2.79 1/h, 0.25 h, 0.042 1/h, 16.51 h, 300.00 mL/kg, 14.00 mL/h/kg, and 364.99 μg.h/mL, respectively. For the calculation of BA values at the same condition, the data obtained from intravenous injection were also iterated based on a non-compartmental model, and the corresponding parameters of λz, t1/2λz, Vz, Cl, and AUC0-144 were 0.019 1/h, 36.26 h, 480.00 mL/kg, 9.10 mL/h/kg, and 514.45 μg.h/mL, respectively. However, there was a considerable difference in the same parameter when calculated by compartmental and non-compartmental approaches. Finally, the medium BA value of DC was evaluated to be 43.84%. This study provides future studies with a framework for determining the BA of DC in the development of a new formulation and provides information on the appropriate use of DC in aquaculture.
Highlights
Doxycycline (DC) is a semi-synthetic broad-spectrum antibiotic belonging to the tetracycline class
The ultra-performance liquid chromatography (UPLC) method of DC was validated by specific indices of limit of detection (LOD), limit of quantification (LOQ), selectivity, linearity, recovery, and precision
The matrixmatch calibration curve was established across concentrations of 0.05–20.0 μg/mL, with good linearity by the coefficient of correlation (R2 = 0.999)
Summary
Doxycycline (DC) is a semi-synthetic broad-spectrum antibiotic belonging to the tetracycline class. DC possesses higher lipophilicity and permeability that results in extensive tissue disposition and long elimination half-life of the drug to efficiently kill pathogens [1] Based on these merits, DC has been approved for use in aquaculture against Aeromonas hydrophila, Edwardsiella ictalurid, and Vibrio in numerous countries, including China, Japan, and the Philippines [2]. The intensified culture method has become increasingly popular to improve the production of channel catfish This approach results in serious problems in aquaculture: (a) water qualities progressively deteriorate due to the residue of formula feed; (b) fish are in poor health due to high culture density and excess nutrient intake; (c) fish diseases can develop, and occur in a restricted culturing environment in response to weather and temperature changes, as well as other stress factors. DC is a good candidate for the treatment of this disease
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